The applicant is a neuroimmunologist with molecular biology and functional genomics experience, and an interest in immune cell-activation mechanisms. His training in neuroimmunology and functional genomics was completed at the Brigham and Women's Hospital (BWH), Boston, MA. He also holds an appointment as an Assistant Professor of Neurology at Harvard Medical School. His interest is now focused on the application of DNA microarrays to establish markers of disease activity in peripheral blood and tissues. The scientific goal of this proposal is to explore the gene expression profile of immune cells in amyotrophic lateral sclerosis. Our hypothesis is that ALS is a complex neurodegenerative disease with a prominent immune component, and understanding of the role that the immune system plays in the disease may lead to new therapies. The Specific Aims are: 1) To perform genechip experiments of peripheral blood mononuclear cells of patients with ALS, other neurological diseases, and normal controls; 2) perform confirmatory northern blots, FACS analysis and TaqMan assays to identify patterns of gene expression that may indicate a) immune system dysfunction, or b) other metabolic changes that may give clues to ALS pathogenesis, and 3) perform comparative analysis of our results in peripheral blood with our other DNA microarray data (currently ongoing) of gene expression in ALS spinal cords and brains, for posting in a web site for public use. The applicant's training in functional genomics, molecular biology and cell immunology will allow him to further explore the critical role of genes whose regulation is altered in ALS. The R21 RFA Award will provide the necessary support for accomplishing these aims.